抗肿瘤剂。125. 4'-O-去甲基-4-脱氧鬼臼毒素的新型4β-苯甲酰氨基衍生物和4'-O-去甲基鬼臼毒素的4β-苯甲酰衍生物作为人DNA拓扑异构酶II的有效抑制剂
Antitumor agents. 125. New 4 beta-benzoylamino derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin and 4 beta-benzoyl derivatives of 4'-O-demethylpodophyllotoxin as potent inhibitors of human DNA topoisomerase II.
作者信息
Zhou X M, Wang Z Q, Chen H X, Cheng Y C, Lee K H
机构信息
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27514.
出版信息
Pharm Res. 1993 Feb;10(2):214-9. doi: 10.1023/a:1018978525533.
A series of 4 beta-benzoylamino (5-17) derivatives of 4'-O-dimethyl-4- desoxypodophyllotoxin and 4 beta-benzoyl (18-20) derivatives of 4'-O-demethyl podophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 5-13 and 15-17 are more potent than etoposide in causing DNA breakage, while compounds 9, 10, 13, 14, 16, and 20 are more active than etoposide in their inhibition of the human DNA topoisomerase II. The order for the enzyme inhibitory activity of the derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin is 4 beta-arylamino > 4 beta-benzylamino > 4 beta-benzoylamino.
已合成了一系列4'-O-二甲基-4-脱氧鬼臼毒素的4β-苯甲酰氨基（5-17）衍生物和4'-O-去甲基鬼臼毒素的4β-苯甲酰基（18-20）衍生物，并对它们抑制人DNA拓扑异构酶II的活性以及引起细胞蛋白连接的DNA断裂的活性进行了评估。化合物5-13和15-17在引起DNA断裂方面比依托泊苷更有效，而化合物9、10、13、14、16和20在抑制人DNA拓扑异构酶II方面比依托泊苷更具活性。4'-O-去甲基-4-脱氧鬼臼毒素衍生物的酶抑制活性顺序为4β-芳基氨基＞4β-苄基氨基＞4β-苯甲酰氨基。
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